title: Impact of CYP2D6 and CYP3A4 genetic polymorphism on combined cholinesterase inhibitors and memantine treatment in mild to moderate Alzheimer's disease.
abstract: OBJECTIVE
  The impact of CYP2D6 and CYP3A4 polymorphism on the steady-state plasma concentrations and therapeutic outcome of donepezil monotherapy and combination therapy in Alzheimer's disease (AD) patients.
  
  
  METHODS
  A total of 38 patients for donepezil and 17 patients for donepezil and memantine therapy, aged ≥ 55 years, were recruited meeting inclusion and exclusion criteria. Polymerase chain reaction-restriction fragment length polymorphism was performed. The liquid chromatography-tandem mass spectrometry method was used for estimation of drug levels of donepezil and memantine.
  
  
  RESULTS
  Significant allele frequency was observed for CYP2D6*3 polymorphism in patients on donepezil monotherapy and combination therapy. Significant allele frequency for CYP2D6*4 was observed in the patients on donepezil monotherapy.
  
  
  CONCLUSIONS
  CYP2D6 polymorphism, though not significant, might partially be involved in the plasma concentration of AD drug.
authors.affiliation: Department of Neurobiochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Sonali
authors.forename: Manjari
authors.initials: M
authors.lastname: Tripathi
authors.forename: Rajesh
authors.initials: R
authors.lastname: Sagar
authors.forename: Thirumurthy
authors.initials: T
authors.lastname: Velpandian
authors.forename: Vivekanandhan
authors.initials: V
authors.lastname: Subbiah
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000097:blood / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D060825:Cognitive Dysfunction / Q000188:drug therapy / Q000523:psychology; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004247:DNA / Q000235:genetics; D039721:Diagnostic and Statistical Manual of Mental Disorders; D000077265:Donepezil; D015259:Dopamine Agents / Q000097:blood / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006801:Humans; D007189:Indans / Q000097:blood / Q000627:therapeutic use; D007194:India; D008297:Male; D008559:Memantine / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000097:blood / Q000627:therapeutic use; D010880:Piperidines / Q000097:blood / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000235:genetics; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D015259:Dopamine Agents; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil; D004247:DNA; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D008559:Memantine